Erichsenfunder0782

Based on the results of this study, mild hypothermia promotes endogenous neuroprotective effects through a mechanism related to functional mitochondria released from astrocytes into the extracellular space and transferred into injured neurons.Human G-protein coupled receptor kinase 6 (GRK6) belongs to the GRK4 kinase subfamily of the G protein-coupled receptor kinase family which comprises of GRK1, GRK2, and GRK4. These kinases phosphorylate ligand-activated G-protein coupled receptors (GPCRs), driving heterotrimeric G protein coupling, desensitization of GPCR, and β-arrestin recruitment. This reaction series mediates cellular signal pathways for cell survival, proliferation, migration and chemotaxis. GRK6 is a kinase target in multiple myeloma since it is highly expressed in myeloma cells compared to epithelial cells and has a significant role in mediating the chemotactic responses of T and B-lymphocytes. To support structure-based drug design, we describe three human GRK6 constructs, GRK6, GRK6His/EK, and GRK6His/TEV, designed for protein expression in Spodoptera frugiperda Sf9 insect cells. Decumbin The first construct did not contain any purification tag whereas the other two constructs contained the His10 affinity tag, which increased purification yields. We report here that all three constructs of GRK6 were overexpressed in Sf9 insect cells and purified to homogeneity at levels that were suitable for co-crystallization of GRK6 with potential inhibitors. The yields of purified GRK6, GRK6His/EK, and GRK6His/TEV were 0.3 mg, 0.8 mg and 0.7 mg per liter of cell culture, respectively. In addition, we have shown that GRK6His/TEV with the His10 tag removed was highly homogeneous and monodisperse as observed by dynamic light scattering measurement and actively folded as exhibited by circular dichroism spectroscopy. The described methods will support the structure-based development of additional therapeutics against multiple myeloma.

The present study used histogram analysis values derived from T1- and T2- weighted (w) images to elucidate possible associations with Tumor-infiltrating lymphocytes (TIL) and Vimentin expression in head and neck squamous cell cancer (HNSCC).

Overall, 28 patients (n=8 female patient, 28.6%) with primary HNSCC of different localizations were involved in the study. Magnetic resonance imaging (MRI) was obtained on a 3T MRI. The images were analyzed with a whole lesion measurement using a histogram approach. TIL- and vimentin-expression was calculated on biopsy samples before any form of treatment.

Several T1-derived parameters correlated with the expression of TIL within the stroma compartment mean (r=0.42, p=0.025), p10 (r=0.50, p=0.007), p25 (r=0.42, p=0.025), median (r=0.39, p=0.036), and mode (r=0.39, p=0.04). No T2-derived parameter correlated with the TIL within the stroma compartment. Several T2-derived parameters correlated with the expression of TIL within the tumor compartment mean (r=-0.52, p=0.004), max (r=-0.43, p=0.02), p10 (r=-0.38, p=0.04), p25 (r=-0.53, p=0.004), p75 (r=-0.52, p=0.004), p90 (r=-0.48, p=0.009), median (r=-0.52, p=0.004), mode (r=-0.40, p=0.03). Kurtosis derived from T2w images had significant higher values in tumor-rich tumors, compared to stroma-rich tumors, (mean 5.5±0.5 versus 4.2±1.2, p=0.028).

Histogram analysis parameters derived from T1w and T2w images might be able to reflect tumor compartments and TIL expression in HNSCC.

Histogram analysis parameters derived from T1w and T2w images might be able to reflect tumor compartments and TIL expression in HNSCC.

To investigate the potential of diffusion kurtosis imaging (DKI) for the assessment of renal fibrosis in chronic kidney disease (CKD), using histopathology as the reference standard.

Eighty-nine CKD patients and twenty healthy volunteers were recruited in this study. DKI was performed in all participants and all CKD patients received renal biopsy. The values of mean diffusivity (MD) and mean kurtosis (MK) in the renal cortex and medulla were compared between CKD patients and healthy volunteers. The Spearman correlation coefficient was calculated to assess the relationship between MD, MK values and the estimated glomerular filtration rate (eGFR), serum creatinine (SCr), 24h urinary protein (24h-UPRO), histopathological fibrosis score.

The medullary MD values were significantly lower than cortex, while the cortical MK values were significantly lower than medulla for all participants. Renal parenchymal MD values were significantly lower in the CKD patients than healthy controls, whereas MK values were significantly higher in the CKD patients than healthy controls. In the CKD patients, the significantly negative correlation was observed between the renal parenchymal MD values and the 24h-UPRO, SCr, histopathological fibrosis score, as well as between the renal parenchymal MK values and the eGFR, while the significantly positive correlation was found between the renal parenchymal MD values and the eGFR, as well as between the renal parenchymal MK values and the 24h-UPRO, SCr, histopathological fibrosis score.

DKI shows great potential in the noninvasive assessment of renal fibrosis in CKD.

DKI shows great potential in the noninvasive assessment of renal fibrosis in CKD.

To evaluate the feasibility of High-resolution (HR) magnetic resonance imaging (MRI) of the liver using deep learning reconstruction (DLR) based on a deep learning denoising technique compared with standard-resolution (SR) imaging.

This retrospective study included patients who underwent abdominal MRI including both HR imaging using DLR and SR imaging between April 1 and August 31, 2019. DLR was applied to all HR images using 12 different strength levels of noise reduction to determine the optimal denoised level for HR images. The mean signal-to-noise ratio (SNR) was then compared between the original HR images without DLR and the optimal denoised HR images with DLR and SR images. The mean image noise, sharpness and overall image quality were also compared. Statistical analyses were performed with the Friedman and Dunn-Bonferroni post-hoc test.

In total, 49 patients were analyzed (median age, 71years; 25 women). In quantitative analysis, the mean SNRs on the original HR images without DLR were significantly lower than those on the SR images in all sequences (p<0.